Cancer Staging and Grading

Once a malignancy has been diagnosed it is essential to know whether it has spread beyond the original site. This staging process is necessary for your doctor to determine your prognosis and plan your treatment. Advanced or late stage cancers, for example, are associated with an unfavorable prognosis and are primarily treated with chemotherapy. Early stage tumors, on the other hand, are usually associated with a favorable prognosis and are primarily treated with surgery, although chemotherapy and radiotherapy are sometimes also used as a means of increasing the probability of a cure.

A cancer's stage is generally based on four pieces of information about the original tumor:

size

degree of invasion into nearby tissues

degree of regional lymph node involvement

presence of metastasis to distant areas of the body

The TNM Classification System

Although newer staging protocols have recently been developed for many cancers, the original TNM system is still useful to demonstrate the concept of staging. The TNM classification system was developed as a tool for doctors to stage different types of cancer based on certain standard criteria. In this system, T stands for the primary tumor, N stands for lymph nodes, and M stands for metastasis.

T
refers to the tumor size: the higher the number, the larger the tumor.

While the designations T1 through T4 correspond to specific tumor sizes, their exact definitions will vary depending on the type and nature of cancer being diagnosed. For example, in non-small cell lung cancer, a T1 tumor is defined as being less than 3 cm in diameter, but in thyroid cancer, a T1 tumor is less than 1 cm in diameter.

N
denotes whether the regional lymph nodes (the group of lymph nodes closest to the site of the primary tumor) contain cancer. The status of the nodes is assigned a number to indicate if the tumor has spread to the local lymph nodes, and the extent of lymph node involvement:

NX (regional lymph nodes cannot be assessed)

N0 (no regional lymph node involvement)

N1, N2, N3 (increasing involvement of regional lymph nodes)

As with the T symbols, the designations N1 through N3 will differ depending on the particular type of cancer. For some types of cancer, N1 is the only level of regional metastasis. Others will use all three N levels. See the Focus on box below to learn more about the lymphatic system.

Focus Box: Metastasis and the Lymphatic System

The lymphatic system is a network of channels that resembles a sewer system in many respects. It drains excess fluid containing dead or damaged cells, other debris, toxins and bacteria from the tissues back into the blood vessels. The channels are periodically interrupted by clusters of lymph nodes found throughout the body, particularly in the neck, torso,
axillae
(armpits) and groin. As it passes through these lymph nodes, the lymph fluid is exposed to numerous specialized cells of the immune system (
lymphocytes
) that clear the fluid of the “trash”. Cancer cells leaving the site of a primary tumor quickly encounter a lymph channel, which carries them to the nearest lymph node cluster. For example, as breast cancer spreads, the cells are collected by the lymph channels in the breast and are taken to the axillary lymph node on the same side. This is why surgeons routinely remove many of these lymph nodes in that location to see if the cancer has already spread. Eventually, the cancer cells can reach the bloodstream where they may be transported to distant sites throughout the body.

M
indicates the absence or presence of distant metastases (spread of cancer to other parts of body via the bloodstream):

MX (presence of distant metastasis cannot be assessed)

M0 (no distant metastasis)

M1 (distant metastasis present)

A letter is sometimes added to the M to show the areas involved. P, for instance, would indicate pulmonary, meaning that the cancer had spread to the lungs.

Putting T, N, M Together

Oncologists may combine the T, N, and M classification to determine a cancer’s stage. For example, in breast cancer, a T1, N0, M0 cancer (small tumor, no nodal involvement, no distant metastasis) is considered a stage I tumor, while a T2, N1, M0 cancer (medium sized tumor, regional lymph node involvement, no distant metastasis) is considered a stage II tumor. Most cancers have four stages:

Stage I

Stage II

Stage III

Stage IV

Stage I tumors are relatively small and have not spread to the lymph nodes or metastasized. On the other hand, Stage IV tumors are relatively large, have spread to the regional lymph nodes, and have metastasized to distant sites in the body. The images below illustrate these various stages.

Image 1: Stage I and Stage II Breast Cancer

Image 2: Stage III and IV (Metastatic) Breast Cancer

The TNM system has undergone numerous revisions as more is learned about how various cancers behave in the body. In addition, blood (hematologic) cancers, such as the leukemias, require staging systems that reflect their unique nature. To learn more about how a specific cancer is staged, click here to link to
In Depth Reports
and find the particular cancer you are interested in.

Grading Tumors

A tumor’s grade describes how closely cancer cells resemble their normal counterparts. This is also referred to as cancer cells’ degree of differentiation. (See the Focus box below for a brief discussion of the importance of cell differentiation in cancer.) Some cancer cells are well differentiated and thus resemble normal cells, while others are poorly differentiated and bear little resemblance to normal cells. In general, the more poorly differentiated the cancer cells the worse the prognosis. In one system, the symbols used to classify tumor grade are:

GX (grade not assessable)

G1 (well differentiated)

G2 (moderately differentiated)

G3 (poorly differentiated)

G4 (undifferentiated); in other words, extremely poorly differentiated and bearing little resemblance to the tissue in which it arose)

Image 5 illustrates the various degrees of differentiation that cancer cells may posses.

Image 5: Tumor Grades

Focus Box: Cell Differentiation and Tumor Grading

Dedifferentiation
is a process whereby cancer cells lose the distinctive cellular features that are characteristic of the tissues in which they arose. The better differentiated a cancer is, the more it resembles its tissue of origin and the more likely it is that the tumor will be less aggressive. The more poorly differentiated a cancer is, the less it resembles its tissue of origin, and the more likely it is to be aggressive. In poorly differentiated prostate cancer, for example, doctors would find it difficult to identify the cancer cells as coming from the prostate gland if it were not for knowing the site in which the primary tumor is found and without relying on special stains that identify cellular markers found in prostate tissue. Additionally, poorly differentiated cells grow rapidly and without restraint, whereas well-differentiated cells (which closely resemble their tissue of origin) are either unable to proliferate or proliferate at a very slow rate. Aggressive cancers are often characterized by poorly differentiated cells, while less aggressive cancers tend to contain moderately or well differentiated cells.

Revision Information

This content is reviewed regularly and is updated when new and relevant evidence is made available. This information is neither intended nor implied to be a substitute for professional medical advice. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with questions regarding a medical condition.